Ovarian AMH: implications for the diagnosis of premature ovarian failure
In addition to markers such as FSH and inhibin A or B, anti-Müllerian hormone (AMH) has recently received much attention as a marker of ovarian function. It has become clear that AMH is secreted by the postnatal ovary and is specifically produced by the granulosa cells in growing follicles from the primary to the small antral stage (in mice) or the larger antral follicle stage (in women) that have not undergone cyclic recruitment by FSH.
Since AMH is expressed in small growing follicles and not in the larger FSH-dependent follicles, its serum values may be a measure of the size of the primordial follicle pool. Indeed, serum AMH correlated very well with a measure of ovarian reserve, the antral follicle count. We found that AMH nicely decreases in serum from women between the ages of 25 and 50 years and is not detectable in post-menopausal women. In two independent cohorts, AMH was found to be constant during the menstrual cycle and cycle-to-cycle determinations at day 3 of the cycle showed that serum AMH does not change between two consecutive cycles. In young women undergoing chemotherapy treatment, serum AMH was found to correlate with residual ovarian function, while serum AMH is undetectable in the majority of women with premature ovarian failure. In women with normogonadotrophic anovulatory infertility (WHOII), AMH is elevated, especially in those patients exhibiting polycystic ovaries (PCO).
Studies in AMH knockout (KO) mice show that AMH is important for the regulation of the rate of primordial recruitment. Thus, ovaries of AMH KO mice show an increased number of small growing follicles accompanied by a decrease in the primordial follicle stock. These results could be validated in vitro using cultured ovaries from 2-day-old mice, where AMH also inhibited expression of marker genes of growing follicles. A second role of AMH was found to be the attenuation of FSH-sensitivity of small antral follicles. In mice, it is this class of follicles that is selected for further growth to the pre-ovulatory stage. Both in vivo and in vitro, AMH KO follicles were more sensitive to FSH in terms of growth.
These results indicate that AMH is a promising marker for ovarian function: it has a clear functional role in the ovary, it can be determined with great sensitivity in serum and serum AMH levels show excellent correlation to a marker of ovarian reserve, antral follicle count.